Search

The vast majority of primary immunodeficiencies (PIDs) occur due to the defects in cells originating from hematopoietic stem cells, while in some PIDs, there are defects in various genes responsible for non‐leucocyte immune response such as seen in epidermodysplasia verruciformis (EV). EV caused by the mutations in TMC6, TMC8, and CIB1 genes is called "typical." "Atypical" EV may develop in patients with primary immunodeficiencies originating from hematopoietic stem cells, which include severe T‐cell failure, caused by inactivating biallelic mutations of STK4, RHOH, CORO1A, ITK, TPP2, DCLRE1C, LCK, RASGRP1, or DOCK8 genes. Here, we present a family with TMC8 gene mutation leading to disseminated epidermodysplasia verruciformis including laryngeal papilloma and recurrent cutaneous squamous cell carcinomas. Typical EV with impaired local, keratinocyte‐intrinsic immune response should be considered when routine immunological examinations are normal in patients presenting with clinical signs of EV. Although it is not possible to prevent EV lesions, early and appropriate surveillance for malignancy is mandatory. [ABSTRACT FROM AUTHOR]

Objectives: In this study, a histopathological comparison was aimed between platelet-rich plasma (PRP) injection and dexamethasone injection in the prevention of scar formation after vocal fold injury. Materials and methods: Electrocautery was applied to damage the right and left vocal folds of a total of 12 New Zealand rabbits. PRP obtained from the rabbit's own blood was injected into the right vocal fold, and dexamethasone was injected into the left vocal fold. After 8 weeks, the experimental animals were euthanized, and the levels of inflammatory cell infiltration, vascularization, collagen, elastin, and hyaluronic acid (HA) were compared in histopathological evaluation. Results: In statistical comparison of histopathological data obtained; in terms of plasma cell infiltration, vascularization, and edema parameters, statistically significant results were obtained in favor of the PRP group. Although the difference between collagen, elastin and HA, which are critical in vocal fold scar healing, was more positive in favor of PRP, no significant result was revealed in the statistical evaluation. Conclusions: PRP injection in rabbits with vocal fold damage reveals similar characteristics with dexamethasone injection in preventing scar formation. PRP injection has favorable effects on vascularization, prevention of edema, and number of plasma cells. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the HPV positivity rate in patients with laryngeal cancer, and to determine the effect of HPV positivity on survival. An additional aim was to determine if patients with HPV positive laryngeal cancer are more sensitive to chemotherapy and if such sensitivity differs according to chemotherapy protocol.Methods: The study included laryngeal specimens obtained from 82 laryngeal cancer patients and 11 laryngeal specimens with normal laryngeal mucosa that were obtained from our hospital's paraffin block archives between 1995 and 2013. HPV was detected via chromogenic in situ hybridization (cISH) and confirmed via genotyping.Results: HPV was not detected in any of the 82 laryngeal cancer patients' laryngeal specimens, nor in any of the 11 archived laryngeal specimens with normal laryngeal mucosa via cISH. Genotyping confirmed these findings; none of the HPV types studied were detected in any of the specimens. As none of the study samples were HPV positive, it was not possible to compare survival, recurrence, or chemotherapy sensitivity.Conclusions: HPV infection is not a leading cause of laryngeal cancer; however, additional research on HPV positivity in patients with laryngeal cancer and its effect on recurrence, survival, and chemotherapy sensitivity is warranted. [ABSTRACT FROM AUTHOR]

Copyright of ENT Updates is the property of Continuing Education & Scientific Research Association (CESRA) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: Epidermal growth factor receptor mutation analysis in non-small cell lung cancer is important for selecting patients who will receive treatment with tyrosine kinase inhibitors. In this study, we aimed to investigate the prevalence of epidermal growth factor receptor mutations and mutation patterns in the Turkish population. Methods: We retrospectively reviewed molecular pathology reports of 959 cases with lung cancer analysed for epidermal growth factor receptor mutations. We analysed all four epidermal growth factor receptor exon mutations using a real-time polymerase chain reaction platform. Results: In this study, the epidermal growth factor receptor mutation rate in the Turkish population was 16.7% (160 of 959). The epidermal growth factor receptor mutation frequency was significantly higher in women (37.1%, n=96) than in men (9.1%, n=64) (p<0.001). In addition, the epidermal growth factor receptor mutation rate was higher in the adenocarcinoma histologic type (p<0.001). Patients with mutations were older than those without mutations (p=0.003). The most frequent mutations were exon 19 deletions (48.8%, 78/160) and exon 21 L858R point mutations (38.1.1%, 61/160). We also detected compound mutation patterns in three cases (1.9%). Conclusion: The prevalence of epidermal growth factor receptor mutations in the Turkish population was slightly higher than that in the Caucasian population and lower than that in the East Asian population. The results of this study may provide guidance in personalized therapy of non-small cell lung cancer in the Turkish population. [ABSTRACT FROM AUTHOR]

Objective: Programmed death ligand 1 (PD-L1) found on tumor cells has recently been reported to have a key role in the development and dissemination of many tumors, such as lung and breast carcinomas. In this study, we retrospectively analyzed PD-L1 expression among different types of sarcomas. Material and Method: Tissue microarrays of 3-4 mm diameter were composed from paraffin blocks of 222 various sarcomas. Slides prepared from microarrays were stained for PD-L1 antibody (Cell Signaling, E1L3N®) using Leica Bond Autostainer. Any membranous staining over 5% of the cells was regarded as positive. Quantitative real-time PCR with TaqMan gene expression assays for PDL1 was performed using whole sections from FFPE tissue of PD-L1 positive cases, by normalizing absolute values to ß-actin. Relative expression level of mRNA of PDL1 was calculated and scored using Log102(threshold cycle of b-actin - threshold cycle of PDL1).. Results: Immunohistochemically, PD-L1 expression was present in 34 of 222 (15%) sarcomas. 5/13 (39%) undifferentiated pleomorphic sarcomas, 6/18 (33%) malignant peripheral nerve sheath tumors, 5/16 (31%) dedifferentiated liposarcomas, 4/19 (21%) rhabdomyosarcomas, 2/16 (13%) epithelioid sarcomas, 2/15 (13%) leiomyosarcomas, 3/26 (12%) synovial sarcomas, 1/18 (6%) myxoid liposarcoma, 1/2 (50%) extraskeletal myxoid chondrosarcoma, 1/3 (33%) alveolar soft part sarcoma, 1/3 (33%) parachordoma/myoepithelioma, 1/5 (20%) pleomorphic liposarcoma, 1/7 (14%) angiosarcoma, 1/8 (13%) Ewing sarcoma showed PD-L1 expression. Cases of solitary fibrous tumor/hemangiopericytoma (18), desmoplastic round cell tumor (14), Ewing-like sarcoma (6), epithelioid hemangioendothelioma (5), clear cell sarcoma (4), myxofibrosarcoma (4), low grade fibromyxoid sarcoma (2) were all negative. Tumor-infiltrating hematopoietic cells were positive for PD-L1 in 32 cases (15%) with only 2 cases overlapping with PD-L1 staining in tumoral cells. Sixteen of 34 (47%) immunohistochemically PD-L1 positive cases showed significant but low-level PD-L1 mRNA overexpression. Conclusion: We have shown PD-L1 expression in a subset of sarcomas, both at the protein and mRNA level. High-grade pleomorphic sarcomas tend to show more frequent PD-L1 expression. Clinical trials are necessary to further assess the effect of anti PD-L1 drugs on sarcomas showing PD-L1 expression. [ABSTRACT FROM AUTHOR]

Epithelioid malignant peripheral nerve sheath tumor ( MPNST) is a rare, relatively less chemosensitive sarcoma. We report clinicopathologic features of 11 epithelioid MPNSTs, including rare forms, along with INI1 immunostaining and BRAF V600E mutation results. BRAF V600E mutation was tested by Real-time polymerase chain reaction ( PCR) technique. Eleven tumors occurred in six men and five women (M:F ratio = 0.85:1) within an age range of 5-73 years (average = 44), mostly in lower limbs (five), followed by upper limbs (four). Tumor size (n = 6), varied from 3.1 to 15 cm (average = 8.3). Histopathologically, most tumors were multilobular, characterized by epithelioid to round-shaped, malignant cells, along with spindle cells (three cases), 'rhabdoid-like' cells (seven cases) and pleomorphic giant cells (single case). By immunohistochemistry, tumor cells were positive for S100 protein (11/11) (100%), EMA (3/7) (42.8%), pan CK(2/7) (28.5%), and HMB45 (1/11) (9%), while these were negative for Melan A (0/11) and INI1 (3/11), including a single tumor, displaying HMB45 positivity. BRAF V600E mutation was positive in 1/8 cases, that lacked melanocytic marker expression. All patients (n = 5) were treated by surgical resection. During follow-up (n = 8, median duration = 23 months), four patients developed tumor recurrences and four developed metastasis, mostly to lymph nodes (3). Finally, four patients were alive with disease, two were alive with no evidence of disease, and two patients died of disease. Epithelioid MPNSTs have a diverse histopathologic spectrum. Loss of INI1 is useful, including in identifying rare forms of epithelioid MPNST, displaying melanocytic differentiation. Most tumors are treated by surgical resection. Loss of INI1 and the presence of BRAF V600E mutation in some cases raises future possibility of exploring targeted therapy in those, rare epithelioid MPNSTs. [ABSTRACT FROM AUTHOR]

We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER, PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, κ statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The κ values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas. [ABSTRACT FROM AUTHOR]

Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the "molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values. [ABSTRACT FROM AUTHOR]

Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the 'molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values. [ABSTRACT FROM AUTHOR]

We aimed to compare the genetic background of different areas in follicular variant papillary thyroid carcinomas (FVPTC) with or without classical nuclear changes. Sixteen cases of FVPTC were included in our study. All tumors were well demarcated from surrounding thyroid tissue and had both areas with nuclear features (WNF) and areas without nuclear features (WONF) of papillary carcinoma. DNA is obtained by laser microdissection from WNF and WONF areas of each case. Point mutations for NRAS codon 61, HRAS codon 61, and BRAF were investigated by direct sequencing. In 11 cases, reverse transcription PCR was performed for the presence of PAX8-PPARɣ and RET/PTC1-3 gene rearrangements. Point mutation for NRAS codon 61 was also studied in 15 colloidal nodules. Seven cases (44 %) showed at least one mutation; two cases (13 %) revealed the same mutation in both WNF and WONF areas, while in the rest only WNF areas were mutated. None of the studied 11 cases demonstrated RET/PTC1-3 gene rearrangement and in only one case PAX8-PPARɣ gene rearrangement was found. Six cases (38 %) showed NRAS codon 61 mutation, involving only WNF areas in five cases and both WNF and WONF areas in one case. Neither HRAS codon 61 nor BRAF mutations were present. Fifteen colloidal nodules were also wild type for NRAS codon 61. Our findings suggest that NRAS codon 61 point mutations and PAX8-PPARɣ gene rearrangement play a role in the FVPTC pathogenesis and may be established before the morphological/phenotypical features fully develop. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Pathology is the property of Turkish Journal of Pathology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Turkish Journal of Pathology is the property of Turkish Journal of Pathology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A 5-month-old female infant was noted to have difficulty in fixating with the left eye with accompanying progressive exo-deviation and axial proptosis. She also had optic disc hypoplasia with the double ring sign. Computed tomography showed left superomedial orbital mass without any orbital bony defect. Incisional biopsy through a medial orbitotomy allowed significant reduction in tumor burden except for the most apical portion. The affected eye resumed normal alignment and full motility. Histopathologically, the tumor was composed of glial tissue intermixed with muscle fibers. Immunohistochemically, desmin and glial fibrillary acidic protein were strongly expressed. Minimal proptosis of the left eye heralded the recurrence of the tumor 4 years later, also confirmed by magnetic resonance imaging studies. This patient embodies the rare occurrence of isolated heterotopic glial tissue in the orbit with skeletal muscle as one of its components and optic disc hypoplasia as the associated ocular anomaly. Late recurrence may occur following incomplete tumor removal. [ABSTRACT FROM AUTHOR]

Presented herein is a case of diffuse fatty infiltration of amyloid goiter in a 58-year-old woman with chronic renal failure. Bilateral total thyroidectomy was performed due to symptoms of dysphagia and hoarseness. Macroscopic and microscopic examination showed that almost all thyroid follicles were replaced by fat cells. Hyalinized stroma intervening the fatty infiltration was shown to harbor amyloid deposition. [ABSTRACT FROM AUTHOR]

Objective: In this study we hypothesized that if timing of gamma probe-guided parathyroidectomy were individualized according to an optimal-time-to-surgery technique, in vivo characterization of parathyroid lesions would be possible. We compared our findings with an ex vivo counting method (“20% rule”) and frozen section results. Study design and settings: Thirty-five patients who were referred for surgical treatment of hyperparathyroidism were studied. Maximum parathyroid to thyroid sestamibi uptake ratio (URmax) was measured by use of preoperative dynamic scintigraphy. The interval between sestamibi injection and URmax was defined as the optimal time to surgery. On the day of surgery, the patients received the same dose of sestamibi and were taken to the operating room at URmax as determined by preoperative scintigraphy. Intraoperative in vivo gamma probe counts from parathyroid lesions were compared with in vivo contralateral background thyroid counts (in vivo/Bkg) and to ex vivo parathyroid counts relative to postexcision background of the adjacent normal tissue (ex vivo/Bkg). Results: A total of 70 excised lesions were evaluated. In vivo/Bkg counts obtained from parathyroid adenoma were significantly different from parathyroid hyperplasia (z = −3.093, P = 0.002) and other lesions (z = −3.958, P = 0.0001). By receiver operating characteristic curve (ROC) analysis, we found the cutoff value for the in vivo/Bkg counts ratio to be 103% to differentiate parathyroid adenoma from hyperplasia with a sensitivity, specificity, and accuracy of 82.5, 65, and 74.4%, respectively. On the other hand, sensitivity, specificity, and accuracy of the ex vivo/Bkg method to differentiate parathyroid adenoma from hyperplasia with a cutoff value of 34.7 was found to be 70.8%, 60%, and 65.9%, respectively. The difference between the accuracy of these 2 tests was not significant statistically (P = 0.137). Sensitivity of frozen section to differentiate parathyroid adenoma and hyperplasia was 76.2% and 33.3%, respectively. Conclusions: Patient-specific optimal protocol for timing of sestamibi injection together with in vivo/Bkg method is a useful alternative method in guiding the surgeon to differentiate parathyroid adenoma from parathyroid hyperplasia and other tissues and may help surgeons’ decisions during the operation. Combined use of in vivo/Bkg and ex vivo/Bkg methods may give more accurate results than frozen section. EBM rating: C-4 [Copyright &y& Elsevier]

Discusses the composition of Schwannomas as common benign tumors and differentiated neoplastic Schwann cell. Identification of the mature adipose and hematopoetic elements that resemble bone marrow; Performance of the ultrasonic imaging and computed tomography scanning; Mixture of spindle cell tumor and myelolipoma characterized by mature adipocytes and hematopoetic cells.

The case of a 33-year-old-woman with a recent onset of left upper eyelid swelling is described. Imaging studies demonstrated a cystic lesion in the left lacrimal gland fossa. Excisional biopsy of the mass showed a dermoid cyst entirely surrounded by a thin layer of normal lacrimal gland tissue. The authors present a highly unusual case of a soft tissue orbital dermoid cyst arising from the lacrimal gland. [ABSTRACT FROM AUTHOR]

Background: Infantile myofibromatosis is a proliferative disorder of infancy and early childhood characterized by the development of single or multiple nodular lesions arising from cutaneous or subcutaneous tissue, muscle, bone or visceral organs. In approximately one-third of cases, this myofibroblastic proliferation involves the head and neck region. Case report: In this paper we report on three cases of cranial infantile myofibromatosis in infants. The clinical presentation and the deceptive histopathological features can make diagnosis difficult. Conclusion: The significance of recognizing this entity is stressed, since its indolent clinical behavior might prevent diagnosis. [ABSTRACT FROM AUTHOR]

The RET finger protein (RFP), which belongs to the B box zinc finger protein family, has a tripartite motif consisting of a Ring finger, a B box finger and a coiled-coil domain. The RET finger protein becomes oncogenic when its tripartite motif is fused with the tyrosine kinase domain of the RET protein. This study examined the RFP expression in normal and tumor tissues by immunohistochemistry. RFP was detected in the nuclei of various cells, including peripheral and central neurones, hepatocytes, adrenal chromaffin cells and male germ cells. Among them, RFP was expressed at high levels in male germ cells such as primary spermatocytes and round spermatids, and formed a perinuclear cap structure in primary spermatocytes. On the other hand, high levels of cytoplasmic expression of RFP were observed in some plasma cells as well as solitary plasmacytoma and multiple myeloma. These results suggested that different nuclear/cytoplasmic distributions of RFP might play a role in the regulation of growth or differentiation of different cell types. [ABSTRACT FROM AUTHOR]

Langerhans' cell histiocytosis (LCH), previously known as Histiocytosis X, is characterized by abnormal accumulations of large mononuclear cells forming granulomas in various organs, mainly bone, skin and lung. This case report describes a 50-year-old man with a history of left pneumonectomy due to squamous cell carcinoma (SCC). During routine follow up, a CXR showed new parenchymal nodules in the right lung 57 months post treatment. Chest CT scan confirmed the presence of multiple parenchymal nodules. Open lung biopsy from the right upper lobe was performed and LCH was diagnosed. Re-analysis of the initial pneumonectomy specimen revealed no evidence of LCH in the surrounding lung tissue. On diagnosis, the patient stopped smoking and was treated with vinblastine and prednisolone for LCH. The nodules disappeared and have not returned in a further 18 months of follow up. In this patient LCH was diagnosed after SCC, which highlights that smoking-related diseases can be seen concomitantly or sequentially in the same patient. [ABSTRACT FROM AUTHOR]

Testicular germ cell cancer is a common cancer in young adults and its incidence has risen dramatically over the past several decades in Western countries. Because RET finger protein (RFP), which belongs to the large B-box RING finger protein family, has been reported to be expressed in different stages of spermatogenesis, we investigated its expression in testicular germ cell tumors. These comprised 13 pure seminomas, five pure non-seminomatous germ cell tumors (NSGCT) and seven mixed germ cell tumors, four of which contained seminomatous component. In normal adult testis, the expression of RFP was strong in the germ cells, particularly in spermatogonia and primary spermatocytes. RFP immunoreactivity was seen uniformly and specifically in 12 of the 13 pure seminomas examined. It was also detected in seminomatous components of mixed germ cell tumors, whereas pure NSGCT were negative for RFP expression. The expression of RFP in male germ cells and seminomas together with the lack of its expression observed in highly aggressive NSGCT suggested that RFP could be associated with the regulation of germ cell proliferation and/or histological-type of germ cell tumors. [ABSTRACT FROM AUTHOR]